Body fluid sampling device

ABSTRACT

Body fluid sampling device comprising a sampling element having a fluid pathway ( 11 ) for receiving body fluid, at least a portion of the fluid pathway is open to the environment and further comprising a fluid receiving means ( 40 ) being spaced from the fluid pathway so that fluid in the pathway will not contact the fluid receiving means initially. The fluid receiving means has two or more test zones ( 45 ) for performing analytical reactions. Fluid from the channel is contacted with the fluid receiving means either by bringing the fluid receiving means and the fluid into mechanical contact or by electrically transporting fluid from the channel onto the fluid receiving means.

REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/469,123, filed Aug. 31, 2006, which is a continuation ofInternational Application No. PCT/EP2005/002316 filed Mar. 4, 2005,published on Sep. 15, 2005 as WO 2005/084545 A1, which claims thebenefit of European Patent Application No. 04005385.2, filed Mar. 6,2004, which are incorporated by reference in their entirety.

BACKGROUND

The present invention relates to the field of body fluid analyses inorder to make a diagnosis or to monitor the concentration of multipleanalytes such as the blood glucose, lactate, cholesterol, lipids etc.

The invention concerns a device and system for sampling small amounts ofsample fluid. A body fluid testing device comprises a sampling elementwith a fluid pathway for receiving sample fluid therein. At least aportion of the fluid pathway is open to the environment. The testingdevice further comprises a fluid receiving means which is separated fromthe fluid pathway so that fluid in the pathway will not contact thefluid receiving means in a first state. The device or system can bebrought into a second state in which at least a portion of the pathwaycontacts the fluid receiving means so that fluid is transferred. Thefluid receiving means comprises two or more test zones each adapted tothe detection of a particular analyte. Based on signals from a sensor ofthe fluid receiving means analyte concentrations can be determined.

Systems for sampling body fluids are already known in the prior art inwhich body fluid is taken up into a disposable element. Blood collectionand analytical systems are e.g. known from the document EP 0 199 484which comprise a disposable unit with a capillary to collect body fluidand to transport the body fluid into a detection area. The furtherdevelopment of this concept is described in WO 97/42888. The arrangementdescribed in this patent is particularly suitable for collectingrelatively small amounts of body fluids which is primarily accomplishedby pressing a ring onto the area surrounding a collection site and apump movement. A system for analysis based on small amounts ofinterstitial fluid is known from EP 0 723 418. For this purpose a verythin closed hollow needle is inserted into the dermis and interstitialfluid is conveyed through the needle to a test zone by applying pressureto the area surrounding the puncture site. A highly miniaturizedarrangement which also utilizes a closed needle to withdraw body fluidis known from U.S. Pat. No. 5,801,057. A particular advantage of thisarrangement is the extremely thin needle which can be inserted into thearm region of a patient without essentially any pain.

Whereas the arrangement described in U.S. Pat. No. 5,801,057 alreadyfulfils numerous practical requirements, some features are in need ofimprovement. A general problem with the sampling devices according tothe previously mentioned document is to manufacture the hollow needlecost-effectively and as small as possible.

With this aim body fluid samplers which have an open fluid pathwaystructure are contemplated. The documents US 2003/0018282 and US2003/0028125 both describe skin piercing devices which have an openchannel for body fluid sampling which at least partially is located in aregion of a piercing needle. Body fluid sampled into the fluid pathwayis transferred to a testing zone which is fixed to the skin piercingelement. In particular US 2003/0028125 describes that the skin piercingelement is integral with a part of a test strip. A further document thatcontemplates a similar sampling and testing device with provision of apooling area is described in US 2002/0168290.

SUMMARY

The prior art sampling and testing devices describe embodiments wheresample from a capillary channel is directly transferred to a testingzone which is in contact with the channel. Contrary to that the presentinvention proposes body fluid sampling and testing devices where thefluid pathway in a phase in which sample is taken up is out of fluidiccontact with a testing zone. After having taken up a fluid sample intothe fluid pathway at least a portion of the fluid pathway is beingcontacted with a fluid receiving means that receives fluid from thepathway. The fluid receiving means itself may comprise two or more testzones or it may be a zone that transports sample to two or more testzones. Wetting of the test zones therefore can be initiated in acontrolled manner by the contacting step. This triggering of test zonewetting has the advantage that the reaction time (i.e. the time betweencontacting a test chemistry with sample fluid and reading of testresults) can be controlled which leads to higher accuracy of analytedetermination. A further advantage compared to the prior art samplingdevices is that fluid sampling and contacting of the sampling elementwith a testing zone can be conducted at different locations. Fluidsampling for example can be done at the front end of a hand-heldapparatus while contacting with a testing zone can be made within theapparatus. Due to this shuttle function of the sampling element opticsor other evaluation means can be moved into the interior of a housingwhich is advantageous with view to the limited space at the front end. Afurther advantage of contacting the test zone or the fluid receivingmeans with sample already present in the fluid pathway is that contactcan be made with a portion of the fluid pathway that does not containthe first fluid emerging the body. By this, influences of plasma andsubstances from the body surface can be avoided or reduced.

Furthermore when the sampling element is a skin piercing element aphysical separation of the test zones from blood during the samplingstep avoids that test chemistry diffuses into the human body.

The present invention which employs a fluid receiving means comprisingtwo or more test zones further provides the advantage that more than oneanalytical test can be made after having made one sampling step. Due tothe order of operations, i.e. the filling of a capillary and contactingthis capillary with the two or more test zones it can be ascertainedthat the test zones are provided with sample fluid in virtually the samemanner. This is advantageous over embodiments where sample is receivedat one end of a cascade of test zones since in this prior art embodimentthe sample fluid is changed by the previous test zones before reaching asuccessive test zone. Further undesired filtering and diffusionprocesses may occur.

Further two or more fluid receiving means each holding one or more testzones can be contacted with the same sampling element. Contacting of thefluid receiving means with the sampling element can be e. g. madesimultaneously or subsequently.

One particular field of application of systems and devices forwithdrawing small amounts of body fluid is the so-called spot-monitoringin which the concentration of particular analytes present in body fluidsis determined at a particular time. Such measurements can be carried outrepeatedly at time intervals in order to monitor a change of analyteconcentration.

The present invention is particularly advantageous for performingso-called panel tests where simultaneously multiple tests are performed.Such panel tests are e.g. known to test lipids, cardiac parameters,liver parameters or other combinations of parameters to determine basicblood constituents as e.g. glucose, lactate, cholesterole,triglycerides, urea, uric acid, creatinine Further immunological testscan be performed where an analyte in the sample fluid interacts with anantibody. Various detection systems are known for such immunologicaltests which e. g. involve coloured markers allowing to detect if ananalyte is present or to measure its concentration.

Test zones are provided on the fluid receiving means which are adaptedto perform analytical testing for a specific parameter. Adaption meansthat the test zones comprise a test chemistry which allows specificdetection of a particular parameter.

Alternatively to having two or more test zones for different analytes ona fluid receiving means, two or more zones for the same analyte can beprovided, e. g. for statistical reasons or the zones can be optimizedfor different analyte concentrations.

The present invention enables the process of analytical testing to begreatly simplified.

Simplification is reached by employing a sampling element which receivesbody fluid in a fluid pathway and this fluid then can be automaticallycontacted with a fluid receiving means including a test zone. Asimplification of testing not only is advantageous for current users, ithopefully also has the effect that more people will do testing of bloodor urine parameters on a regular basis.

A sampling device and system according to the present invention servesto withdraw small amounts of body fluid. In this context body fluids areunderstood in particular as blood, interstitial fluid and mixtures ofthese body fluids. Whereas in conventional blood collection systems thisis usually carried out on the finger pad, the collection systemaccording to the invention can also be used to withdraw blood fromalternate sites on the body such as the forearm and the palm. In apreferred embodiment the sampling element is a skin piercing element.

A skin piercing element for withdrawing small amounts of body fluidaccording to the present invention has a protruding portion with asharpened end for piercing skin. Within at least a region of theprotruding portion a fluid pathway is located which has a capillaryactivity to transport body fluid. At least a part of the capillarystructure, preferably the whole capillary, is open to the outside alongits extension. A capillary structure is understood within the scope ofthe invention as a body which transports body fluid as a result ofcapillary forces towards the proximal end of the capillary structurewhen the distal area is contacted with body fluid. With regard to thisfunction the capillary structure according to the invention is similarto the open needle structures described in US 2003/0018282 and US2003/0028125 to which reference is made herewith. However, an importantdifference is that these documents describe microneedles where thecapillary channel is steadily in fluidic contact with a test zone sothat body fluid received in the capillary channel is directly applied tothe test zone and hence initiates reaction.

The longitudinal extension of the skin piercing element extends from aproximal end which provides a holding area to a distal end having aprotruding portion which is intended to be inserted into the skin. Thehollow needles of the prior art have an opening at their distal endthrough which body fluid can enter and the fluid pathway then changesinto a closed channel or chamber in which the test zone is located. Incontrast the capillary structure according to the present inventionpreferably is open to the outside over its entire longitudinal extensionand the fluid path is not closed by a test zone.

Open capillaries can be manufactured by photolitho-graphic methods likethose described in the document U.S. Pat. No. 5,801,057 and which areknown from the field of semiconductor technology. It is also possible toprovide channels, grooves etc. which are open to the outside in solidneedles by milling, etching and such like. The capillaries can also beformed in plastics during manufacturing as e.g. micro injection molding.Depressions which provide the capillary channel may lead from the tip orat least from a region adjoining the sampling tip respectively the skinpiercing element to a proximal holding region which is connectable to aholding device. The depressions or capillaries do not necessarily haveto run in straight lines, but can also for example be arranged inspirals, meanders etc. Furthermore the capillaries may be arranged in anetwork with bifurcations, split capillaries, etc.

In accordance with the present invention where the fluid receiving meanscomprises two or more test zones it is preferred when the capillarysplits into smaller channels so that the sample fluid is laterallyextended. In such cases contacting of the two or more test zones thencan be best done by contacting different sub-channels with the differenttest zones.

In a further embodiment two or more fluid receiving means each havingone or more test zones can be contacted with the same sampling element.

The cross-section of the capillaries can for example be V-shaped,semi-circular or also rectangular.

Such channels are preferably generated by etching processes asphotochemical milling (PCM). PCM is the machining of metal structureswithout heating or mechanically milling the starting material. PCM isbased on optical pattern transfer and etch processes. It is known to bea micromachining technology.

The starting materials are metal sheets. There is a wide range ofdifferent materials to choose from, ranging from medical steel toaluminium and invar. In the case of steel, most of the standard medicaltypes are available. When compared to silicon, glass or quartz, the costof the raw material steel is much lower.

PCM is a Photolithography based fabrication method, i.e. the outline ofa structure to be machined is transferred optically. A photosensiblepolymer is applied onto the metal sheet in a film. The polymer isreferred to as photoresist and comes in two types:

-   1. Dry resist (foil laminated onto the substrate)-   2. Wet resist (liquid spread and cured on the substrate)

Upon selective illumination of the photoresist via a shadow mask, thephotoresist can be selectively removed from the substrate (which isoften referred to as patterning).

When the patterned substrate is exposed to aqueous solution (e.g. Iron(III) chloride for steel) which reacts with the substrate material, thematerial is selectively removed from the areas where there is nophotoresist left (referred to as the “etch”). There are two mainprinciples of how the substrate can be brought in contact with thesubstrate.

-   1. dipping of the substrate into a bath of etchant-   2. spraying of the etchant on the substrate

The etch step is in its nature generally isotropic, i.e. the etch rateis approximately the same in all directions. Isotropicity can beinfluenced by a large number of parameters during the photolithographyand during the etch, thus it is possible to control the etch profilewithin certain limits.

Spray etching offers larger flexibility in controlling etch rates andprofiles when compared to dip etching.

In most cases, it is imperative that the photoresist layer is removedfrom the substrate to obtain the sampling devices. Removal ofphotoresist layer is normally a wet process.

In addition to the already mentioned methods for incorporating capillarychannels into surfaces, it is also possible to generate the capillarychannels by assembling bodies in a way that capillary gaps are created.Thus it is for example possible to fasten two or more solid needlestogether for example by welding such that the contact areas of the solidneedles form capillary channels. In a corresponding manner it is alsopossible to twist wires together in the form of a stranded wire suchthat numerous contact areas are formed which generate the capillarychannels. Further skin-piercing elements with fluid pathways can becreated by applying one or more layer of materials (e.g. laminatedfoils) onto a flat needle in a way that a capillary gap is createdbetween the layers or is provided in one such layer.

The capillary channels which provide the fluid pathway typically have agreater depth than width. The ratio of depth to width (generallyreferred to as aspect ratio) is preferably 0.3 to 3. The cross-sectionof the capillary channel is typically larger than 2500 μm² and less than1 mm². Preferably the capillary channel has a width in the range of 50to 450 micrometers, most preferred around 200 micrometers. As alreadystated above it is advantageous that the capillary channels are open tothe outside such that they can take up body fluid while the capillarystructure is inserted into the body. In order to achieve a good uptakeof body fluid the area of the capillary structure that is open to theoutside should have a length of 0.5 mm or more.

The shape of a skin piercing element is relatively uncritical. It canfor example be in the form of a small cube. Special measures are usuallynot necessary to mount the skin piercing element in a drive unit but aholding region located at the proximal end of the skin piercing elementis preferred. Advantageously the holding area is formed integral withthe other regions of the skin piercing element. Piercing element designscan be employed that are known for disposable lancets of conventionalblood sampling systems. For example the holding region can have tapersinto which spring elements of a holder of a drive unit engage in orderto hold the piercing element. The piercing element is advantageouslypositioned within a holder in such a manner (for example by pressing theend of the piercing element facing away from the tip against a stop)that it allows a good control of the piercing depth. Reference is madeto the document EP B 0 565 970 with regard to such a holder and theinteraction between the holder and the disposable lancing unit.

The body fluid testing device in addition to the sampling element has afluid receiving means which is spatially separated from the fluidpathway of the sampling element so that fluid in that pathway will notcontact the fluid receiving means during filling. The fluid receivingmeans and the pathway, however, are contacted to each other after fluidsample has been received in at least a part of the fluid pathway andwhen start of the analytical reaction is desired.

The spatial separation of sampling element and fluid receiving meansenables embodiments where the sampling element is employed as a shuttleto transport sampled fluid to a fluid receiving means. This isparticularly advantageous when fluid sampling is made in a spatiallyrestricted area (e.g. the front end of apparatus) and the fluidreceiving means does not fit well into this limited space. The latter inparticular is the case for fluid receiving means fixed to a tape as e.g.described in European patent application 0 202 6242.4, U.S. Pat. No.4,218,421 and EP 0 299 517. The shuttle function enables a testingprocess with the steps of

-   -   sampling body fluid into the sampling element    -   transporting sampled body fluid with the sampling element to a        fluid receiving means    -   contacting the fluid receiving means with body fluid on the        sampling element,    -   detecting a change of the fluid receiving means which relates to        the concentration of two or more analytes.

When a magazine with fluid receiving means is employed there further canbe the steps of exposing a specific fluid receiving means from thestored fluid receiving means to contact the sampling element loaded withsample fluid. When the specific fluid receiving means has been evaluateda further fluid receiving means can be exposed to contact sample fluidon sampling element.

A system according to above shuttle concept therefore has one or moresampling elements and a transport means to transport the samplingelement into contact with a fluid receiving means. The sampling elementmay be a skin piercing element and the system then has a suitabledriver. The drive for piercing and the transport means may be employedin the same drive unit. Further the system may comprise a storage unitfor multiple fluid receiving means. The system further may comprise anexposing unit for successively exposing fluid receiving means to receivefluid.

The fluid receiving means is a structure that can take up fluid from afluid pathway of the sampling element. This uptake of fluid e.g. can beaccomplished by an electrical potential applied between fluid in thefluid pathway and the fluid receiving means. Preferably, however, thefluid receiving means has a higher capillarity than the fluid pathway ofthe skin piercing element so that during contact fluid is automaticallytaken up. In this regard the fluid receiving means can be made from afleece or fabric material that has a high capillarity and is hydrophilic(at least in areas for fluid take-up). The fluid receiving means mayhave a particular region which comprises such material of highcapillarity or the whole area of the fluid receiving means can act asreceiving means for fluid from the fluid channel. The fluid receivingmeans may virtually only comprise two or more test zones which can becovered with a fabric or woven material or the fluid receiving means maybe more complex and allows for pre-processing of sample fluid and/ortransport of fluid to sensor/test zones. Pre-processing may comprisefiltration of fluid sample and/or a mixing with reagents. The test zonese. g. can be spotted or printed onto a substrate to obtain a fluidreceiving means with analytical capability.

The fluid receiving means comprises two or more test zones with achemistry layer that contains reagents for detecting two or moreanalytes.

The reagents undergo a detectable change due to reaction with theanalyte to be detected. Typical reagents for detecting glucose are basedfor example on glucose oxidase in conjunction with a chromogenic redoxsystem. Reagents are well known in the prior art for optical evaluationwhich form a colour with glucose from the body fluid. Furthermorereagents are also known from the field of blood sugar test strips whichallow electrochemical detection of analytes. The reagent mixtures thatare used are usually in a solid state and, due to their constituents(e.g. aluminium oxide, kieselguhr and such like), have such a highcapillarity that they can take up body fluid from the capillary channel.Since these detection systems are well-known from the prior art they arenot described in more detail herein but reference is made to U.S. Pat.No. 5,762,770 and U.S. Pat. No. 36,268. Similar test systems are knownfor various other analytes.

When the sampling element is a skin piercing element the body fluidcollection system according to the present invention additionally has adrive unit which, when activated, moves the skin piercing element from afirst into a second position such that it performs a lancing movement.Suitable drive units are well-known from the field of blood samplingsystems. It can for example contain a spring which is cocked by the userand when released drives the skin piercing element. A particularlyadvantageous drive unit is described in EP B 0 565 970.

Systems for body fluid analysis comprise a detection unit. If asensor/test zone containing reagent is used which changes colour orforms a colour when an analyte is present, the system can have anoptical detection unit comprising a light source and a detector todetect transmitted or reflected light.

According to the present invention the fluid receiving means has two ormore test zones. These can be evaluated by the same optics in a way thatthe fluid receiving means and the optics are moved to one another sothat the test zones are successively read. Further it is possible toemploy optics with multiple detection channels so that the two or moretest zones can be evaluated simultaneously.

When electrochemical detection is employed, the system has electrodeswhich contact the test zone or the fluid receiving means. For evaluationof raw signals the system can have electronic devices known in the priorart in order to determine the concentration of analyte for example bymeasuring the so-called Cotrell current (see e. g. U.S. Pat. No.36,268). Other detection principles may also be employed as well as acombination of different detection principles for evaluation of the testzones.

With the skin piercing element according to the present invention bodyfluid can be withdrawn while the protruding portion is inserted into theskin (i.e. withdrawal of sample directly from the body and/or from bodyfluid emerging on the body surface) or the protruding portion can beretracted from the body after piercing and takes up body fluid thatemerges on the body surface. A partial withdrawal in which theprotruding portion remains in the body but the lancing channel in theskin is opened to collect body fluid is especially suitable for samplingat the arm. This is due to the fact that small incisions on the armclose very rapidly such that no fluid or only very small amounts offluid emerge after piercing. On the other hand the sensitivity to painis much less pronounced on the arm as compared for example to the fingerand thus when the protruding portion remains in the body this is notfelt to be painful. As described above an advantage of a capillarystructure that is open to the outside is that fluid can be taken upthrough the open fluid channel whereas the area for taking up liquids byhollow needles is limited to the front end of the needle. The latter isparticularly disadvantageous when the needle opening becomes sealed bytissue (due to a stamped out tissue portion) during the piercing processsuch that no liquid or only an inadequate amount can be taken up.

Furthermore a withdrawal process can be carried out with the samplingdevice according to the invention which is a combination of thepreviously mentioned processes. In this combined process piercing iscarried out firstly, the protruding portion is pulled back over a partof the piercing path and is allowed to reside there for a collectionperiod of few seconds. An advantage of this process is that theretraction of the protruding portion exposes a part of the lancingchannel such that body fluid collects therein and can enter from thereinto the fluid pathway of the skin piercing element. Further suchwithdrawal process has the advantage that blood on the skin surface canbe taken up by the open channel. Depending on the circumstances it mayeven be possible to remove residual blood almost completely so that noblood is seen by the user.

A further decisive factor which is important for an efficient uptake ofbody fluid into the fluid pathway is the wettability of the capillarychannel. When capillary structures made of silicon are used, these areusually adequately wettable due to a silicon oxide layer on the surface.If metals or plastics are used for the capillary structure, these areoften relatively difficult to wet. This can be counteracted by a numberof different measures such as silication of the surface. The wettabilityis usually adequate when the liquid in the capillaries has a concavemeniscus which is the case when the wetting angle is less than 90°. Thepresent invention will be described in more detail with regard to thefigures. The description of specific embodiments as shown in thefigures, however is not intended to limit the scope of the presentinvention.

BRIEF DESCRIPTION OF DRAWINGS

The present invention will be described in more detail with regard tothe figures, in which:

FIG. 1A schematically shows a first embodiment of a skin piercingelement with a moveable fluid pathway in a perspective view;

FIG. 1B shows the FIG. 1A embodiment with a fluid receiving meansincluding a test zone in a perspective view;

FIG. 1C shows the FIG. 1B embodiment with the moveable portion incontact with the test zone in a perspective view;

FIG. 2A shows a further embodiment with a moveable fluid receivingmeans;

FIG. 2B shows a portion of the fluid channel from the FIG. 2Aembodiment;

FIG. 2C shows the test zones near or in contact with the fluid pathwayof the FIG. 2A embodiment;

FIG. 3A shows a cross-sectional view of a further embodiment of apiercing element, a test zone, and a hydrophobic coating;

FIG. 3B shows a cross-sectional view of another embodiment of a piercingelement and test zones;

FIG. 3C shows a cross-sectional view of a third embodiment of a piercingelement and test zones;

FIG. 3D shows a cross-sectional view of a fourth embodiment of apiercing element and test zones;

FIG. 4A illustrates the concept of electrical triggering a contact ofsample fluid;

FIG. 4B shows two embodiments of collecting zones;

FIG. 5A depicts a design for providing a skin piercing element and atest zone in spaced apart geometry;

FIG. 5B depicts another embodiment of a design for providing a skinpiercing element and a test zone in spaced apart geometry;

FIG. 5C depicts yet another embodiment of a design for providing a skinpiercing element and a test zone in spaced apart geometry;

FIG. 6 schematically shows an improved shape of the capillary channel;

FIG. 7A shows a skin piercing element having regions with differentcross section in a first configuration after skin has been pierced;

FIG. 7B shows the FIG. 7A embodiment in a second configuration after theskin piercing element is contacted with a carrier;

FIG. 8A shows a first embodiment of a skin piercing element which isadapted to provide sample fluid to multiple test zones; and

FIG. 8B shows a second embodiment of a skin piercing element which isadapted to provide sample fluid to multiple test zones.

DESCRIPTION OF SELECTED EMBODIMENTS

For the purpose of promoting an understanding of the principles of theinvention, reference will now be made to the embodiments illustrated inthe drawings and specific language will be used to describe the same. Itwill nevertheless be understood that no limitation of the scope of theinvention is thereby intended. Any alterations and further modificationsin the described embodiments, and any further applications of theprinciples of the invention as described herein are contemplated aswould normally occur to one skilled in the art to which the inventionrelates.

FIG. 1 shows a skin piercing element (10) which has a fluid pathway (11)which runs in an elongated portion (12, 13) of the skin piercingelement. This portion is connected to a holder (14) in form of a frame.The elongated portion has a protruding portion (12) which protrudes fromthe holder portion (14). At the front end of the protruding portion asharpened tip (15) is located. The sharpened tip (15) enablespenetration of the skin surface during pricking with the skin piercingelement. The fluid pathway (11) starts in the front end region of theprotruding portion and extends into a movable portion (13) which islocated in the holder frame (14). The fluid pathway is an open capillarychannel which permits body fluid which contacts the channel in theregion of the protruding portion to move into the moveable portion (13)by means of capillary action. As depicted in FIG. 1A protruding portion,moveable portion and frame portion of the skin piercing element areformed integrally. The skin piercing element (10) can be made by etchingprocesses. As well known in silicon manufacturing processes a wafer ofsilicon material can be etched to provide devices comprising tips andcapillary channels. For mass production it is however advantageous toproduce the skin piercing elements by etching of thin metal plates. Itis particularly advantageous that the sharpened tip (15) of theprotruding portion (12) can be formed during the etching process as wellso as to avoid separate grinding steps.

As can be seen from FIG. 1A there is no reagent or sensor contacting thefluid channel which would receive body fluid immediately after thechannel has been filled with sample fluid. The present inventioncontrary to that proposes to locate a test zone or sensor separately ona fluid receiving means.

FIG. 1B shows the skin piercing element (10) of FIG. 1A together with afluid receiving means including a test zone. The fluid receiving means(40) is shown schematically. The fluid receiving means (40) is locatedon the upper side of the skin piercing element on which side the fluidchannel (11) is open to the environment. The fluid receiving means (40)is, however, initially spaced from the fluid pathway (11) so that samplefluid within the fluid pathway does not contact the fluid receivingmeans. Therefore no fluid transfer from the fluid pathway onto the fluidreceiving means occurs in this geometry of the fluid sampling device. Inthe depicted embodiment the fluid receiving means essentially consistsof a holding structure (41) which provides proper orientation andspacing of the fluid receiving means relative to the skin piercingelement and three test zones (45, 45′, 45″). In the depicted embodimentthe test zones comprise different reagent chemistries which produceoptical signals based on the concentration of three analytes in the bodyfluid. Due to the incorporation of porous materials as e.g. kieselghuror titanium dioxid the reagent chemistry already has high capillaritythat sucks fluid from capillary channel (11). The reagent chemistriesare applied to a carrier surface. As shown in FIG. 1B initially thefluid pathway and the test zones (45, 45′, 45″) are spaced apart so thatbody fluid located in the capillary channel (11) will not be transferredto the test zones (45, 45′, 45″). After fluid has been received in thefluid pathway and has filled the moveable section (13) the body fluidsampling device is primed for measurement. By means of mechanicalactuation the moveable section (13) can be bend in direction of the testzones so that body fluid located in the fluid pathway contacts the testzones and wets the reagent chemistries. This mode of contacting the testzones with sample fluid has several advantages over the prior artdevices.

A first advantage over the prior art is that measurement can beinitiated at a specific point in time. This means that the time betweenwetting of the test zones and measurement of the final signal can bechosen at will. The time period, however, is shorter than the dryingtime of blood in the capillary. Knowing or controlling the time ofreaction improves accuracy of the measurement. Further a signal can bemeasured beginning directly after wetting which allows to monitorreaction kinetics. Evaluation of this early signals can be used toimprove accuracy of the measurement result as well. A further advantagecan be seen from FIG. 1B. When the moveable section (13) is contactedwith the test zones (45, 45′, 45″) it contacts an intermediate sectionof the fluid channel (11) but not the very end. Fluid contaminated bythe skin surface or containing interstitial fluid (ISF) enters thecapillary first and therefore resides after filling in the end portionof the capillary. Fluid in this end portion is not contacted with thefluid receiving means, therefore the end portion is called dischargeregion. The intermediate portion of the channel therefore contains fluidalmost uncontaminated and without ISF. Since fluid from this region istransferred to the fluid receiving means and therefore needs to beaccessible, this region is called the access region. This concept oftransporting fluid from the capillary to the fluid receiving meansserves to exclude disturbances of measurement by plasma or substancesfrom the skin surface. It goes by its own that contamination bysubstances from the skin surface should be avoided if possible, inparticular, when the amounts of sample for analysis are decreased to lowamounts (e.g. below 1 microliter). For interstitial fluid it is knownthat this body fluid normally does not show the actual blood analyteconcentrations but concentrations from 5 to 30 minutes before. This isdue to the time delay of exchange between the blood compartment and theinterstitial fluid compartment.

It has to be understood that this concept which avoids to contact thefluid receiving means with (contaminated) fluid received first in thechannel can be applied to a number of device designs and is notrestricted to sampling devices having a skin piercing element. Thisinvokes a method of sampling fluid comprising the steps of

-   -   introducing fluid into an introduction region of a support        structure which has a channel therein, said fluid filling an        access region of the support structure which is accessible from        the surrounding and the channel having a discharge region        located downstream the access region    -   contacting a fluid receiving means with fluid located in the        access region to receive fluid but not contacting it with fluid        in the discharge region.

But now back to the embodiment shown in FIG. 1 where the supportstructure is a skin piercing element. The contacting between themoveable portion (13) and the test zones (45, 45′, 45″) can be seen inFIG. 1C. As this figure shows, the moveable portion due to its shape inform of a tongue can be bent upwardly. Based on the very thin structureof the skin piercing element the moveable section automatically willhave enough flexibility if the skin piercing element is made from aductile material. Suitable materials are e. g. metals, silicon and evenceramics which do not brake upon bending.

It has to be considered, that instead of bringing the capillary to thetest zones it is also possible to bring the test zones to the capillaryby e. g. bending the carrier.

FIG. 2A shows a second embodiment where contact between the fluidchannel and the fluid receiving means is accomplished by a moveablefluid receiving means. As in the first embodiment the skin piercingelement has a protruding portion (12) with a tip (15) for piercing theskin. A fluid channel (11) in form of a capillary channel starts closeto the piercing tip (15) and extends into an intermediate section of theholder portion (14). The fluid receiving means comprises a spacer (42)and a moveable carrier (43) fixed to the spacer. The moveable carrier(43) at its underside holds two test zones (45, 45′) in form of areagent matrix for optical detection. When the capillary channel (11) isfilled with sample fluid the moveable carrier (43) is depressed and thetest zones (45, 45′) contacts the filled channel and take up body fluid.The transparent carrier (43) now can be illuminated and radiationreflected by the back side of the test zones (45, 45′) can be measuredto obtain a signal.

FIG. 2B shows the portion of the fluid channel (11) which contacts thesensors (45, 45′) in more detail. As can be seen the channel hasupstanding walls which protrude from the upper surface of the skinpiercing element (14). The upstanding walls (11′) have pointed edges.The function of these edges can better be seen in FIG. 2C which showsthe interaction between a test zone and the fluid pathway (11). The leftdrawing of FIG. 2C shows the test zones (45, 45′) approaching the fluidpathway. The test zones (45, 45′) are located at the underside of acarrier (40). The body fluid (25) residing in the fluid pathway (11) hasa depressed conus. This means that a slight contact between the testzones and the walls of the fluid pathway may not be sufficient tocontact the body fluid with the testing material. In the right handdrawing the function of the pointed edges can be seen which serves todepress the sensor material or even to cut it. Due to this the testzones on one hand are approaching the surface of body fluid more closelyand on the other hand an intimate contact between the testing materialand the channel walls is achieved. Both aspects improve transfer of bodyfluid from the fluid pathway onto the test zone.

FIG. 3 depicts four embodiments showing cuts through piercing elementsand test zones. This will illustrate a technical problem which has to beaccounted for. In FIG. 3 a an embodiment is shown where a hydrophobiccoating (16) has been applied on the body piercing element beside thefluid channel. As can be seen in FIG. 3 a contact of the test zones withthe skin piercing element does not only bring the test zones and bodyfluid into contact but during the contact capillary spaces are generatedbetween the test zones (or the carrier) on one hand and the portionsbeside the fluid pathway on the other hand. This normally creates a highcapillarity which transfers sample fluid residing in the channel notonly on the test zones but also into the small capillary spaces whichare generated. The hydrophobic coating (16) avoids sample fluid fromcreeping between the upper surface of the skin piercing element (14) andthe carrier or test zones. It is desired to transfer the sample onto adedicated area of the testing material so that the transferred amountsof sample fluid are sufficient to wet the test zones in a way that anaccurate measurement can be achieved. Loosing sample fluid to otherregions of the test zones or to the carrier could mean that the testingmaterials are not wetted sufficiently in the dedicated regions andmeasurement cannot be conducted properly.

FIG. 3 b shows a further embodiment which avoids an unintentionalcreeping of sample fluid. Similarly to FIG. 2 this embodiment hasupstanding channel walls which contact the test zones or the carrier.Due to this, fluid that creeps into spaces stops at the outer channelwalls and a loss of sample fluid is largely reduced. The channel walls,however, do not need to be square shaped as depicted in FIG. 3 b butthey may also be pointed as shown in FIG. 3 c or 3 d.

FIG. 4 shows the concept of electrical triggering a contact of samplefluid with the test zones.

This general concept, however, is shown in FIG. 4 with respect to a skinpiercing element as special embodiment of a support structure having achannel. For fluid triggering a high potential is applied between thesample fluid (25) and the carrier (40). This may cause either samplefluid to move from the channel onto the test zones or may cause amovement of the carrier in direction of the channel. In both caseswetting of the test zones by sample fluid can be triggered in a veryshort time frame by turning on the electrical potential. As can be seenby transparent drawing of the carrier the channel beneath the test zonesleads into a collecting zone (26) for providing a larger amount of fluidfor wetting the test zones than the thin capillary channel wouldprovide.

FIG. 4B depicts preferred embodiments of collecting zones in moredetail. As can be seen the collecting zone (26) preferably hasupstanding elements (26′) which facilitate movement of fluid onto thetest zones. These upstanding elements on one hand provoke highelectrical charges at their end for transporting fluid and on the otherhand they improve capillarity of the collecting zone (26) which improvesfilling with fluid.

FIGS. 5A, B and C depict sampler designs for providing skin piercingelement and test zones in a spaced apart geometry that allows contactingof test zones with sample fluid in the channel by actuation. Theembodiment of FIG. 5A is similar to FIG. 1. The skin piercing elementcomprises a frame which is connected to an inner portion (13′) in whichruns the capillary channel (11). Inner portion and frame are connectedby bendable portions (51). After filling of the capillary channel theinner portion is torsioned against the frame so that a portion of thecapillary contacts the test zones beneath the carrier (43). By bendingaround the bendable portions the inner portion contacts the test zonesin an angled manner. This has proven to be particularly advantageoussince it provides a uniform wetting of the test zones without inclusionof air bubbles.

FIG. 5B shows an embodiment where the carrier (43) and its support areconnected via bendable portions (51′) to a main portion (14′) whichcomprises the capillary. Again contact between capillary and test zonesis accomplished in a tilted manner.

FIG. 5C shows an embodiment having an inner portion (13″) which isconnected at two ends to the frame portion (14″). When pressure isapplied from the underside to the central part of the inner portion(13″) this bends against the test zones beneath the carrier (43). Bybowing this inner portion again an angled contacting is achieved.

FIG. 6 schematically depicts an improved shape of the capillary channel.It has been found that the fill level of fluid in the channel generallyincreases with decreasing width of the capillary. The capillary of FIG.6 has a first region (a) which leads into the tip portion of the skinpiercing element. A second region (b) of increased diameter is forproviding an increased sample volume. Particularly useful is thirdregion (c) of decreased width. Due to the decreased width the fill levelis increased and therefore transfer of fluid from the channel to thetest zones has a high success rate. Therefore it is preferred to contactthe test zones with the capillary in a tilted manner so that it firstcontacts region (c) and thereafter region (b). This ensures that fluidtransfer will be initiated safely by region (c) and enough sample fortesting is provided by region (b). Region (d) downstream region (c) maybe employed to discharge contaminated sample fluid or ISF.

FIG. 7 shows a skin piercing element having a first region (a) leadinginto the tip region and a second region (b) of increased diameter.Picture A shows a status after skin has been pierced and blood was takeninto region (a) of the capillary channel. Due to lower decreasedcapillarity of region (b) sample liquid fills region (a) but not region(b). When the skin piercing element is contacted with a carrier (43) theopen channel structure (a, b, d) in some portion is closed at its topand capillarity is hence increased in this portion so that collectionregion (b) is filled and test zones on the underside of the carrier (43)come into contact with sample fluid. It is advantageous to have acircular detection area with view to the geometry of optical elements.

A skin piercing element according to FIG. 7 may be used in followingmethod:

-   -   piercing skin    -   sampling body fluid into a portion of the capillary channel        (region (a)).    -   contacting the capillary channel in a collecting region (b) with        test zones and/or a carrier so that region (b) fills with body        fluid    -   detecting changes of the test zones due to reaction with analyte        from the body fluid.

FIGS. 8A and 8B show embodiments of skin piercing elements (10) whichare adapted to provide sample fluid to multiple (three in the depictedcases) test zones. The fluid pathways (11) in both figures start in thefront end region near to the sharpened tip (15). For further descriptionof FIGS. 8A and 8B reference is made to FIG. 1. FIGS. 8A and 8B havereservoir zones (47, 47′, 47″) which serve to hold sample for wettingcorresponding test zones when contacted with them. The reservoirspreferably have a larger diameter than the capillary channel (11) sothat a larger amount of fluid is stored. In FIG. 8A the reservoir zonesare integrated into the straight fluid pathway (11) while in FIG. 8Bside channels branching off from the main fluid pathway are providedwhich lead fluid into the reservoir zones. Sampling elements of thepresent invention therefore may have side fluid channels which branchfrom the main fluid pathway and reservoirs provided in these side fluidchannels. According to this the reservoir zones and hence the contactsites with test zones can be separated spatially to avoid interferencesbetween the contact sites.

While the invention has been illustrated and described in detail in thedrawings and foregoing description, the same is to be considered asillustrative and not restrictive in character, it being understood thatonly the preferred embodiment has been shown and described and that allchanges, equivalents, and modifications that come within the spirit ofthe inventions defined by following claims are desired to be protected.

1. A method for determining an analyte concentration in body fluidcomprising the steps of: a) receiving body fluid in a fluid pathway of asampling element, b) providing a fluid receiving means having two ormore test zones, c) moving at least one of the sampling element and thefluid receiving means after said receiving body fluid so that thesampling element and the fluid receiving means contact one another andbody fluid from the fluid pathway of the sampling element contacts saidtwo or more test zones while a fluid bolus first entering the fluidpathway is not contacted with the test zones, d) receiving signals fromsaid at least one test zone which are characteristic for an analyteconcentration, and e) providing a detection unit for processing saidsignals to determine an analyte concentration.
 2. The method accordingto claim 1, wherein a time period beginning with step c) is monitoredand determination of analyte concentration is initiated based on thetime passed.
 3. The method according to claim 1, wherein step c)initiates a monitoring of signals and the change of signal over time isemployed to determine a point in time for concentration determination.4. The method according to claim 1, comprising pricking skin with saidskin piercing element.
 5. A method for determining an analyteconcentration in body fluid comprising the steps of: a) receiving bodyfluid in a fluid pathway of a sampling element, b) moving at least oneof the sampling element or a first test zone to contact the samplingelement with the first test zone so that body fluid from the fluidpathway of the sampling element contacts the first test zone, whereinsaid contacting occurs at an intermediate portion of the fluid pathwayso that a fluid bolus first entering the fluid pathway is not contactedwith the first test zone, c) simultaneously contacting the samplingelement with a second test zone so that body fluid from the fluidpathway of the sampling element simultaneously contacts the second testzone, d) receiving signals from the two test zones, and e) providing adetection unit for processing said signals to determine analyteconcentrations.
 6. A body fluid testing device, comprising: a samplingelement defining a fluid channel, the fluid channel including alaterally open portion with a length, the laterally open portion havingan open side along its length; a test section with at least two testzones for testing body fluid; and a moveable section connected to thesampling element and the test section, the moveable section beingmoveable from a first condition with the laterally open portion of thefluid channel and the test section being out of fluidic contact with oneanother wherein the laterally open portion of the fluid channel cannotcontact the test section to a second condition with the laterally openportion of the fluid channel and the test section being in fluidiccontact with one another wherein the laterally open portion of the fluidchannel contacts the test section.
 7. The body fluid testing device ofclaim 6, with the sampling element further including a skin piercing tipin fluidic contact with the fluid channel.
 8. The body fluid testingdevice of claim 7, with the fluid channel having a fluid introductionregion near said skin piercing tip and upstream from the laterally openportion, and a discharge region downstream from the laterally openportion.
 9. The body fluid testing device of claim 6, further comprisinga bendable portion attached to the moveable section, the bendableportion being configured and adapted to bend as the moveable sectionmoves from the first condition to the second condition.
 10. The bodyfluid testing device of claim 6, wherein the fluid channel and the testsection contact one another in an angled manner when the moveablesection is in the second condition.
 11. The body fluid testing device ofclaim 6, wherein the moveable section is moveable to simultaneouslyplace the two test zones in fluidic contact with the laterally openportion of the fluid channel when moving from the first condition to thesecond condition.
 12. The method according to claim 1, wherein saidcontacting includes contacting the two or more test zones with the fluidpathway in a tilted manner.